Different morphology, stage and treatment affect immune cell infiltration and long‐term outcome in patients with non‐small‐cell lung carcinoma

Souza, Paola da Costa; Parra, Edwin Roger; Atanazio, Marcelo Junqueira; Silva, Osmar Bianchi da; Noleto, Gustavo; Ab’Saber, Alexandre Muxfeldt; Fernezlian, Sandra; Takagaki, Tereza; Capelozzi, Vera Luíza

doi:10.1111/j.1365-2559.2012.04318.x

Cited by 13 publications

(12 citation statements)

References 47 publications

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“…In addition, TILs in NSCLC tissues often display a memory phenotype (27,28), with the evidence of activation (29,30) suggesting that adaptive immune response to neoplastic cells takes place in some NSCLC patients. A key question, addressed only in a few studies (30)(31)(32), is whether tumor-associated T cells are significantly enriched in the surgical tumor sample compared with matched NnL, because activated T cells can be found even in the non-neoplastic lung parenchyma (30,32). In this study, we found a selective enrichment in the tumor for recently activated (HLA-DR þ ) T cells expressing a T EM profile compared with NnL.…”

Section: Discussionsupporting

confidence: 51%

Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non–Small Cell Lung Cancer

et al. 2017

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Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1 þ T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR þ ) T cells with an effector memory (T EM ) profile are enriched in such lesions. Tumor-infiltrating lymphocytes coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3, and TIGIT, but also displayed a recently activated, nonexhausted phenotype. We also identified a subset of CD8þ T lymphocytes at the earliest phase of functional differentiation after priming, termed "early effector cells" (EEC), which also exhibited an activated nonexhausted phenotype, but was less differentiated and associated with coexpression of multiple inhibitory receptors. In response to autologous tumor, EECs upregulated CD107a, produced IL2 and IFNg, and were competent for differentiation. The identification of EECs marked by inhibitory receptor expression at tumor sites will enable investigations of early stages of adaptive antitumor immunity, as well as support the rationale for administering immunotherapy in early-stage non-small cell lung cancer. Cancer Res; 77(4); 851-61. Ó2016 AACR.

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Section: Discussionsupporting

confidence: 51%

Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non–Small Cell Lung Cancer

et al. 2017

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“…A total of 12 out of the 20 included studies used CD68 as macrophage marker [15, 18, 23, 24, 28–30, 32–36], while the other 4 studies used CD68 in combination with other markers for the detection of TAMs [19, 25–27]. Unlike some other solid tumors, the total number of I+S CD68 + TAMs was not associated with survival in lung cancer patients, while low islet and high stromal CD68 + TAMs were both associated with poor OS.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis

et al. 2016

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Tumor-associated macrophages (TAMs) are important components of cancer microenvironment. In the present study, we searched PubMed, Embase, Cochrane library and Web of Science to perform a meta-analysis of 20 studies including a total of 2,572 non-small cell lung cancer (NSCLC) patients, in order to determine the association between TAMs and NSCLC prognosis. The combined hazard ratio (HR) of 9 studies showed that the density of total CD68+ TAMs in the tumor islet and stroma was not associated with overall survival (OS) of the patients. However, the pooled HR of 4 studies showed that high density of CD68+ TAMs in the tumor islet predicted better OS, while the pooled HR of 6 studies showed that high density of CD68+ TAMs in the tumor stroma was associated with poor OS. A high islet/stroma ratio of CD68+ TAMs was associated with better OS. A high density of M1 TAMs in the tumor islet was associated with better OS, while a high density of M2 TAMs in the tumor stroma predicted poor OS. These findings suggest that, although the density of total CD68+ TAMs is not associated with OS, the localization and M1/M2 polarization of TAMs are potential prognostic predictors of NSCLC.

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“…94,95 In a study of 65 patients with NSCLC, squamous tumors were associated with a prominent adaptive immune response, whereas greater innate immune responses were observed in adenocarcinomas and large cell carcinomas. 96 Much recent attention has also been placed on immune checkpoint proteins, in particular the programmed death-1 (PD-1) receptor and its ligand, PD-L1. Initial studies indicate that PD-L1 is expressed in 25-39% of NSCLC tumors, 97,98 although the role of PD-L1 expression as a biomarker is yet to be fully determined.…”

Section: Immunological Profilementioning

confidence: 99%

Clinicopathologic Features of Advanced Squamous NSCLC

Socinski

Obasaju

Gandara

et al. 2016

Journal of Thoracic Oncology

108

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Lung cancer remains the leading cause of cancer-related death worldwide. NSCLC accounts for more than 85% of all lung cancers, and the prognosis for advanced-stage disease is typically poor. In recent years, the importance of histologic subtypes of NSCLC has been recognized, and the distinction between squamous and other NSCLC histologic subtypes is now critical to patient management. Squamous cell lung cancer (sqCLC) represents approximately 25% to 30% of NSCLC. The prognosis for patients with advanced NSCLC is poorer for those with sqCLC than for those with adenocarcinoma. This is partly due to a number of clinical characteristics that distinguish sqCLC from other NSCLC histologic subtypes, such as smoking history, comorbid diseases, age, and molecular profile. Together, these factors make sqCLC an especially challenging disease to manage. Herein, we review some of the key clinicopathologic features of sqCLC. Understanding these features to optimally address many of the unique therapeutic challenges of this disease is likely to be central to ultimately improving outcomes for patients with squamous NSCLC.

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Different morphology, stage and treatment affect immune cell infiltration and long‐term outcome in patients with non‐small‐cell lung carcinoma

Abstract: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.

Cited by 13 publications

References 47 publications

Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non–Small Cell Lung Cancer

Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non–Small Cell Lung Cancer

Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis

Clinicopathologic Features of Advanced Squamous NSCLC

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